ClC-5: ontogeny of an alternative chloride channel in respiratory epithelia

Rebecca D. Edmonds, Ian V. Silva, William B. Guggino, Robert B. Butler, Pamela L. Zeitlin, Carol J. Blaisdell

Abstract

Chloride transport is critical to many functions of the lung. Molecular defects in the best-known chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR), lead to impaired function of airway defensins, hydration of airway surface fluid, and mucociliary clearance leading to chronic lung disease, and premature death, but do not cause defects in lung development. We examined the expression of one member of the ClC family of volume- and voltage-regulated channels using the ribonuclease protection assay and Western blot analysis in rats. ClC-5 mRNA and protein are most strongly expressed in the fetal lung, and expression is maintained although downregulated postnatally. In addition, using immunocytochemistry, we find that ClC-5 is predominantly expressed along the luminal surface of the airway epithelium, suggesting that ClC-5 may participate in lung chloride secretion. Identifying candidate genes for critical ion transport functions is essential for understanding normal lung morphogenesis and the pathophysiology of several lung diseases. In addition, the manipulation of non-CFTR chloride channels may provide a viable approach for treating cystic fibrosis lung disease.

  • ion channels
  • developmental regulation
  • calcium channel family

Footnotes

  • This work was supported by the American Lung Association of Maryland, National Heart, Lung, and Blood Institute Grant K08-HL-03469 to C. J. Blaisdell, and the Short-Term Research Training Program (to R. B. Butler); and the Cystic Fibrosis Foundation, Zeitli96PO (to P. L. Zeitlin).

  • Address for reprint requests and other correspondence: C. J. Blaisdell, Univ. of Maryland Medical System, Bressler 10-019, 655 W. Baltimore St., Baltimore, MD 21201 (E-mail:cblaisdell{at}peds.umaryland.edu).

  • The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • 10.1152/ajplung.00207.2001

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